The long-term goal of this interdisciplinary (numerical engineering modeling, bench-top and clinical experiments) project is to improve the predictability of orthodontic treatment. Predictability will produce reductions in iatrogenic side effects, needed corrections, office visits, and treatment time - all to benefit clinician and patient. The proposed study focuses on the two most used treatment strategies (translation vs. tipping with root correction) for canine retraction, a frequent clinical procedure. The three dimensional (3D) clinical orthodontic load systems will be controlled; the clinical outcomes based on tooth movement theory will be predicted; and the actual clinical outcomes in terms of treatment time, tooth movement, and root resorption will be quantified using newly developed technologies. Biological responses as reflected by local inflammation and bone quality will be monitored. Furthermore, the effect of genotype on clinical outcomes will also be evaluated. The main objectives are to (1) quantitatively evaluate two commonly used, but philosophically divergent, well-controlled orthodontic loading modalities by comparing treatment times and their attendant side effects, and (2) identify the roles of biological factors on the clinical outcomes. The hypotheses are: (H-1) the direct translation path (Strategy 1) needs less treatment time than the indirect pattern (Strategy 2); (H-2) Strategy 1 produces lower stress concentrations; (H-3) the strategy with the lower stress concentration will produce reduced stress-related side effects such as root resorption and inflammatory responses; and (H-4) IL- 12 Allele affects the treatment time of both strategies in a similar way, thus playing an insignificant role in comparison to the differences in the two treatment mechanics. The specific aims (SA) are: SA-1 Characterize and quantify the mechanics of the treatment strategies using our previously developed orthodontic force tester (OFT). SA-2 Quantify the clinical outcomes in terms of 3D tooth displacements assessed from casts of clinical impressions and Conebeam CT (CBCT) images. SA-3 Directly associate treatment strategy mechanics with the clinical outcome. SA-4 Develop a method to quantify orthodontics-associated root resorption and tooth morphology using CBCT data. SA-5 Calculate the mechanical environment in bone, PDL, and root and determine the location of the tooth's center of resistance. SA-6 Treat patients with calibrated orthodontic load systems and quantify the resulting tooth displacements and biological responses. The outcomes of this study will provide clear evidence as to which strategy is superior. They will also provide insight into ways of reducing iatrogenic side effects and into the necessary evidence-based trade-offs for optimized treatment. With the knowledge gained, future orthodontic appliances will be designed to reduce side effects and treatment time. Furthermore, these results will provide a foundation for innovative mechanics that optimize other orthodontic treatments. PUBLIC HEALTH RELEVANCE: The project will clinically evaluate two commonly used treatment strategies on the same patient. Both treatment time and side effects including root resorption will be quantified. The relevance of this project is that it will clinically identify the superior strategy and the directions for improvement.